The Cardiovascular Pathophysiology & Therapeutics Group reflects the combined interests of members of The Queen Elizabeth Hospital’s (TQEH) Cardiology and Clinical Pharmacology groups. This research collaboration has existed for over the past 20 years at TQEH.

We are mainly interested in developing a better understanding of the “new” cardiovascular epidemics of the 21st century, including atrial fibrillation, systolic hypertension, aortic valve disease, stress “Tako-Tsubo” cardiomyopathy and metabolic heart disease. We recognise that these conditions are responsible for impaired quality of life, as well as increased mortality rates. Therefore, we consider the development of effective treatment modalities as a major priority.

Supervised by: Dr Y Chirkov, Dr TH Nguyen and Professor J Horowitz
Angina pectoris is a common and debilitating problem in Western society, usually resulting from narrowing of coronary arteries. However, in a substantial minority of patients, spasm of the large or small coronary arteries is the cause of pain. While this condition can be treated symptomatically, there is no available cure, and many patients have poor quality of life because of frequent and recurrent episodes of pain. We are currently evaluating integrity of signalling pathways related to anti-aggregatory autacoids (e.g. nitric oxide and prostacyclin) in coronary spasm patients, with encouraging pilot results. These ongoing studies may lead to the development of better treatments for this condition.

Supervised by: Dr S Liu and Professor J Horowitz
Chemotherapy-induced cardiotoxicity is an emerging cause of heart failure that could add millions more to the healthcare budget. Currently, there are over 400,000 cancer survivors in Australia and that number is expected to continuously increase. Given that virtually all of the drugs concerned are cardiac toxic, this advance has come at the cost of increased risk of symptomatic or fatal heart failure. Doxorubicin, a member of the anthracycline family, is a well-known chemotherapeutic agent which is used in treatment of a wide variety of cancers. The successful use of doxorubicin has been hampered by toxicities such as hematopoietic suppression, nausea, vomiting, extravasation, and alopecia, yet the most feared side-effect is cardiotoxicity. The planned study will utilize technology which is already established in our laboratory to establish the determinants of extent of toxic effect of doxorubicin compared with those of other more recently developed antineoplastic drugs. The technology will utilize human myocardial cell grown in culture, and will quantitate the transition from complete cell viability through apoptosis to eventual necrosis. The results will help in the development of methods to develop cardiac-safe anticancer therapeutics.

Higher Degree Research Project: Impact of B-type natriuretic peptide (BNP) on stabilisation and function of the myocardium

Supervised by: Dr S Liu, Dr Y Chirkov and Professor J Horowitz
We have recently shown that BNP exerts important anti-inflammatory effects, by stabilising white blood cells and diminishing superoxide production. We wish to determine whether this results in limitation of inflammatory change within the heart, and whether this anti-inflammatory effect of BNP is lost in acute heart failure.

Higher Degree Research Project: The heart in stress: Tako-Tsubo cardiomyopathy

Supervised by Dr TH Nguyen and Professor J Horowitz
Tako-Tsubo syndrome (TS) occurs mainly in ageing women as a dysfunctional, inflammatory response of the heart to adrenaline. We have partially characterised the chemical signal transduction pathway in TS, and now seek to evaluate potential therapeutic avenues, using intact animal models, essentially to characterize the impairment in post-receptor signaling.

Higher Degree Research Project: Defects in physiological regulation of platelet aggregation: implications in the setting of potential coronary stenting

Supervised by Dr Y Chirkov and Professor J Horowitz
We are studying regulation of blood clot formation in patients with different cardiac conditions. Blood clots cause heart attacks and strokes. Clot formation can be prevented with special medications (eg. clopidogrel or ticagrelor), which are used clinically to prevent thrombosis.
Our research is aiming to identify a reason for the frequently occurring less-than-expected response to these medications. We are focusing on platelets because the starting point for blood clot is platelet aggregation. Autacoids, naturally occurring within the organism (e.g. nitric oxide and prostacyclin) which are supposed to control the normal function of platelets, stop working properly in patients with cardio-vascular diseases. It turns out that the platelet adenylate cyclase system is particularly important in predicting responses to clopidogrel and related drugs, implying that defective adenylate cyclase signalling may be the basis for poor patient responses to this class of drugs. We are trying to work out what is going wrong with this regulation and how it could be restored.